This invention is related to a high precision positioning device and a method of operating that may be used in a number of applications and is of particular use with regard to high precision, high density dispensing.
As our ability to analyse smaller and smaller material improves the need for machines that can accurately and repeatably dispense such material increases. In particular there is a need to produce gene arrays accurately and repeatably. A high precision positioning device may be used as a high precision, high density dispensing apparatus. High precision positioning device could be used for a number of applications but it is of particular importance with regard to the production of gene arrays. Accordingly, the following discussion will be framed with regard to gene arrays but such apparatus could be used for any high precision task.
A gene array is a small glass slide on which different DNA samples, in a range of up to 200,000 unique samples, are spotted as an array. The materials used for the samples may range from yeast DNA to human DNA. Preferably the spots are as close as possible so as to facilitate scanning by a suitable microscope reader. The gene array provides the ability to analyze thousands of genes simultaneously so as to speed-read the book of a live being. The arrays are typically used in the diagnosis and treatment of diseases such as cancer. However, as bio-sensors and gene maps, there are a wide range of possible applications in a variety of fields, such as police records, identity cards, agriculture and the like. In addition the apparatus could be used for such applications as microelectronic manufacturing and rapid prototyping.
Typically a gene array requires a very large number, 2,000 to 200,000, of DNA samples to be spotted on a small area, approximately 20 mmxc3x9720 mm. For a typical 6,000 samples or a 78xc3x9778 array of different DNA samples, the centre-to-centre distance between adjacent samples is approximately 0.25 mm and the sample diameter is less than 0.20 mm. Similarly, for a typical 150,000 samples or a 388xc3x97388 array of different DNA samples, the centre-to-centre distance between adjacent samples is approximately 0.05 mm and the sample diameter is less than 0.04 mm.
Preferably the samples are of similar and uniform shape and size so that there is a useful readable image. The quantity of DNA per sample should also be within a close tolerance range (5 nano litres or less depending on the spot diameter). Gene arrays are expensive products and accordingly, the tolerance for error is very stringent.
There are a number of factors which determine the effectiveness of a system for manufacturing gene arrays. Specifically, the precision of the apparatus or robot, the flexibility with regard to the configuration of the dispensing and spotting, and the ability to accommodate various sizes and layouts of source plates are examples of factors that determine effectiveness. The precision of the spotting is very important in regard to the usefulness of the gene array. One factor influencing the precision of spotting is the precision of the robotic system manipulating the dispenser in the three-dimensional space. Further, the configuration of the layouts of samples required for different applications varies widely and an effective system would be able to accommodate various sample layouts. Similarly, the sizes and layouts of DNA source plates mounted near the slide holder platen in the robotic workspace also vary and an effective system would be able to accommodate various sizes and layouts of source plates.
Currently, there are a number of manufacturers that are working on developing gene array production systems. Generally, these gene array systems are automated, but they have no intelligent features to support high-quality dispensing processes or any on-line inspection and monitoring. Further, these systems lack flexibility in terms of sample and slide layouts, and adoption of different dispenser heads for different specific needs. Moreover such systems are limited to low density arrays (up to 10,000 samples). As well, none of these systems includes a representation of the spotting process as a real-time animation. Clearly, this feature allows the user to visualize the progress of production since the minute samples being made on the slides cannot be seen by the naked eye.
Some manufacturers have focussed on the print head designs. For example, Telechem International Inc. has produced a micro-spotting print head called Arraylt(trademark) which allows the user to use between one and thirty-two pins. The Genetic Microsystems Inc. has a spotting system that includes a ring rod and a pin that move independently in the z direction. The ring rod picks up the sample which is held by surface tension. The ring rod is then positioned in the desired x-y location. The pin is driven down through the ring rod, picks up the sample, contacts the slide and deposits the sample o n the slide.
Accordingly it would be advantageous to provide a high precision positioning device and method of operating same that could be used with a dispensing head for manufacturing gene arrays and the like and in addition that could be used with other the end effectors. It would be advantageous to provide a dispensing method and apparatus that is flexible and adaptable to meet a variety of productivity requirements required for reliable gene array production.
Further it would be desirable that the dispensing method and apparatus can be adapted to accommodate different dispensing heads. In addition, it would be advantageous to provide a system that provides a representation of the spotting process as a real-time animation. Still further, it would be advantageous to provide a system that includes on-line inspection and monitoring.
A high precision positioning device includes an end effector and a platen spaced therebelow for receiving a workpiece. One of the end effector and the platen is moveable in the X-Y plane. One of the end effector and the platen is moveable in the Z direction. The device includes senors for sensing the position of the end effector in the X, Y and Z directions relative to the platen. The apparatus includes a control system for controlling the movement of the end effector relative to the platen and adjusting the position of the end effector relative to the X. Y and Z position as sensed by the sensors. Preferably the platen is generally parallel to the X-Y plane and the Z direction is normal to the platen. Preferably the control system uses a position, velocity and acceleration control system for controlling the movement in the X and Y direction and an impedance control system for controlling the movement in the Z direction.
In another aspect of the invention a method of operating a high precision positioning device is provided. The method uses a host computer and an embedded computer. The method includes the steps of receiving and checking data; sending and decoding the checked data and determining when a move command appears; instructing a move command and determining set-point data for the move command; sending set-point data to regulator task module and sending data from the positional sensors to the regulator task module; determining the control parameters in the regulator task module and activating the motors to move the end effector.
In a further aspect of the invention a capillary reel dispenser for use in association with a high precision positioning device is provided. The capillary reel dispenser includes a capillary tube, a capillary reel having the capillary tube wound therearound, a means for advancing the capillary tube and a cutter for cutting off the used portion of the capillary tube.
In a still further aspect of the invention a slide having a plurality of gene material spotted thereon in a density of at least 20,000 spots per centimetre squared is provided.
Further features of the invention will be described or will become apparent in the course of the following detailed description.